Human metapneumovirus (hMPV) is a newly identified paramyxovirus that is associated with respiratory infections in humans. Recent work in our laboratory demonstrates that this virus is one of the top two most frequent causes of lower respiratory tract disease in infants and children, along with respiratory syncytial virus (RSV). Despite the recent discovery of hMPV, rapid progress is being made in study of the basic pathogenesis and immunity of the virus. Based on the high level of genetic relatedness of hMPV to RSV, it is likely that serum neutralizing antibodies to the surface glycoproteins play the dominant role in preventing disease due to hMPV reinfection. Therefore, it is reasonable to think that immunization with a vaccine that presents the surface glycoproteins of hMPV in vaccinees in a conformationally authentic manner may protect against hMPV disease. Past efforts to develop paramyxovirus subunit vaccines or vectored vaccines expressing glycoproteins, however, have been stymied by significant obstacles. We propose to use a novel but established vaccine delivery system (VEE vector) to express hMPV surface glycoproteins and to test the immunogenicity and protective efficacy of the vaccine constructs in small animal models. The VEE vector system offers advantages for respiratory tract immunization designed to elicit mucosal immunity. The consortium submitting this application brings together an experienced investigator group with expertise in pneumovirus and alphavirus virology, immunology, and vaccine development.